Changing T cell specificity by retroviral T cell receptor display

The diversity of the T cell receptor (TCR) repertoire is limited, because o f the processes of positive and negative T cell selection. To obtain T cell s with specificities beyond the immune system's capacity, we have developed a strategy for retroviral ICR display. In this approach, a library of T ce ll variants is generated in vitro and introduced into a TCR-negative murine T cell line by retroviral transfer. We document the value of TCR display b y the creation of a library of an influenza A-specific TCR and the subseque nt in vitro selection of TCRs that either recognize the parental influenza epitope or that have acquired a specificity for a different influenza A str ain. The resulting in vitro selected TCRs induce efficient T cell activatio n after ligand recognition and are of equal or higher potency than the in v ivo generated parent receptor. TCR display should prove a useful strategy f or the generation of high-affinity tumor-specific TCRs for gene transfer pu rposes.